Ординатура / Офтальмология / Английские материалы / Oxford American Handbook of Ophthalmology_Tsai, Denniston, Murray_2011

506 CHAPTER 15 Intraocular tumors

Cryotherapy

Consider for similar small tumors that are equatorial or pre-equatorial.

Radiotherapy

Consider plaque radiotherapy for larger tumors not involving the optic nerve or macula and with only limited vitreous seeding; consider external beam radiotherapy for larger or multiple tumors, optic nerve involvement, or significant vitreous seeding, or when other measures have failed.

Complications include cataract, orbital growth abnormalities, radiation retinopathy, and secondary malignancies (significant risk in patients with germinal mutations).

Chemotherapy

Consider for bilateral disease, large tumors (chemoreduction combined with local treatment), extraocular involvement, metastasis, or recurrence. Common regimens include carboplatin, etopside, and vincristine.

Enucleation

Consider for advanced disease (particularly if unilateral/asymmetric). Aim to remove >10 mm length of optic nerve, which is the main exit route for tumor cells. An implant may be inserted at the initial surgery unless residual tumor is suspected.

Prognosis

Most untreated tumors proceed to local invasion and metastasis to cause death within 2 years; rarely, however, the tumor may spontaneously stop growing to form a retinoma, or necrose to cause phthisis bulbi.

Most small to medium-sized tumors without vitreous seeding can be successfully treated while preserving useful vision. Overall, there is a 95% survival rate (in the developed world).

Poor prognostic factors include size of tumor, optic nerve involvement, extraocular spread, and older age of child. Patients with germinal mutations are at increased risk of pineoblastoma (trilateral retinoblastoma), ectopic intracranial retinoblastoma, and osteogenic or soft tissue sarcomas. Risk is also increased with radiation exposure.

Box 15.4 Differential diagnosis of leukocoria

•Retinoblastoma

•Cataract

•Persistent fetal vasculature syndrome

•Inflammatory cyclitic membrane

•Coats’ disease

•ROP

•Toxocara

•Incontinentia pigment

•Familial exudative vitreoretinopathy

•Retinal dysplasia (e.g., Norrie’s disease, Patau’s syndrome, Edward’s syndrome)

•Other posterior-segment tumors (e.g., combined hamartoma of RPE and retina)

RETINAL HEMANGIOMAS 507

Retinal hemangiomas

Capillary hemangioma

This is an uncommon benign hamartoma of the retinal (or optic disc) vasculature consisting of capillary-like vessels. It may present at any age but is most commonly diagnosed in young adults. Isolated capillary hemangiomas are usually not related to systemic disease, but most multiple and bilateral tumors are seen in the context of von Hippel–Lindau syndrome (VHL) (Table 15.5).

Histologically, there are endothelial cells, pericytes, and stromal cells. The VHL mutation may be restricted to the stromal cells, suggesting that despite their innocent appearance, they are the underlying neoplastic cell.

Clinical features

•dVA; asymptomatic (may be diagnosed on family screening).

•Red nodular lesion with tortuosity and dilatation (often irregular) of feeding artery and draining vein, exudation, exudative retinal detachment, rubeosis/neovascular glaucoma, epiretinal membranes, tractional retinal detachment, vitreous hemorrhage.

•Optic disc hemangiomas are less well defined and do not have obvious feeder vessels.

Investigation

•FA: rapid sequential filling of artery, hemangioma, and vein; extensive late leakage. Leakage into vitreous may appear hazy on late images.

Treatment

Systemic disease

If VHL is suspected, multidisciplinary care with physician and clinical geneticist is required.

Ocular disease

•Photocoagulation for small (<3 mm diameter) tumors requires confluent white burns covering the entire tumor and feeder artery; multiple treatment sessions are usually required.

•Cryotherapy is used for peripheral or larger tumors, usually double freeze-thaw technique. Multiple treatment sessions are often required.

•Radiotherapy.

•Excision.

Table 15.5 Features of von Hippel–Lindau syndrome

508 CHAPTER 15 Intraocular tumors

Cavernous hemangioma

This is an uncommon benign hamartoma of the retinal (or optic disc) vasculature that consists of large-caliber, thin-walled vessels. It is usually isolated but familial bilateral cases do occur.

Clinical features

•Usually asymptomatic; occasional dVA or floaters.

•Cluster of intraretinal blood-filled saccules (a plasma level may separate out due to the slow flow); otherwise normal retinal vasculature; vitreous hemorrhage.

Investigation and treatment

•FA shows slow filling, hyperfluorescence, and no leakage.

•Treatment is not usually necessary.

Racemose hemangioma

These are rare retinal arteriovenous malformations (AVMs) and are therefore not true tumors. Although congenital, they progress with age and are usually detected in early adulthood.

These may be isolated or associated with ipsilateral AVMs of the CNS (Wyburn–Mason syndrome; Table 15.6).

Clinical features

•Usually asymptomatic; occasional dVA.

•Enlarged tortuous vascular abnormality with direct connection between arterial and venous circulations with similar color throughout.

Investigation and treatment

This is usually a clinical diagnosis. There is no effective treatment for retinal AVMs, although intracranial AVMs have been successfully treated with surgery, radiotherapy, and embolization.

Table 15.6 Features of Wyburn–Mason syndrome

OTHER RETINAL TUMORS 509

Other retinal tumors

Astrocytoma

This is a rare, benign tumor of the neurosensory retina that is composed of astrocytes. There is debate as to whether it is acquired or actually a hamartoma. Typically, it presents in childhood or adolescence; both sexes are equally affected.

Isolated astrocytomas are usually not associated with systemic disease, but most multiple and bilateral tumors are seen in the context of tuberous sclerosis (Table 15.7). An association with neurofibromatosis (NF) is also suggested.

Clinical features

•dVA, but often asymptomatic.

•Superficial white, well-defined lesion (translucent to calcified “mulberry” type; flat or nodular), exudative retinal detachment.

Investigation and treatment

Further evaluation is not usually required other than ruling out possible syndromic associations.

Table 15.7 Features of tuberous sclerosis

510 CHAPTER 15 Intraocular tumors

RPE tumors

Congenital hypertrophy of the retinal pigment epithelium (CHRPE)

This is a common benign congenital proliferation of the RPE occurring in around 1% of the population (typical form). The typical form is unilateral and either solitary or, more commonly, grouped (“bear tracks”). They are unrelated to systemic disease. The atypical form is bilateral and multifocal and is associated with familial adenomatous polyposis (FAP) and its variants (Table 15.8).

Histologically, the RPE cells are of increased height with increased numbers of melanin granules.

Clinical features

Typical CHRPE

•Solitary: black, well-defined, flat, round lesion, often with depigmented lacunae within it, deep to the neurosensory retina; usually 2–5 mm.

•Grouped: similar smaller lesions, grouped to form “bear tracks”; usually <2 mm.

Atypical CHRPE

•Bilateral, multiple, widely separated, black oval lesions with irregular depigmentation; usually <2 mm

Investigation and treatment

Typical CHRPE does not require investigation. Atypical CHRPE should prompt an investigation of family history and consideration of referral to a gastroenterologist. If FAP is diagnosed, prophylactic colectomy is recommended. In untreated FAP, the development of colonic carcinoma is almost universal.

Table 15.8 Features of familial adenomatous polyposis (FAP)

Combined hamartoma of the RPE and retina

This is a rare, benign hamartoma of the RPE, retinal astrocytes, and retinal vasculature. It is usually not related to systemic disease but may be associated with NF-2 and, rarely, NF-1 (see Tables 15.9 and 15.10).

Clinical features

•Decreased VA, floaters, leukocoria.

•Elevated lesion with whitish sheen superficially (epiretinal membranes and intraretinal gliosis), tortuous vessels, and variable deeper pigmentation; usually juxtapapillary but may be peripheral; usually 4–6 mm in diameter.

512 CHAPTER 15 Intraocular tumors

Lymphoma

Although this is an uncommon tumor of the eye, ocular lymphoma is increasing in incidence. It is both sight threatening and life threatening and is easily missed, as it may masquerade as a number of other conditions. Risk factors include immunosuppression (e.g., therapy-associated, AIDS).

Epstein–Barr virus (EBV) is strongly associated with ocular-CNS lymphoma in AIDS patients. The cell type is usually large-cell, non-Hodgkin’s B-cell lymphoma, although T-cell NHL is also seen. Two patterns of disease are seen: ocular-CNS and systemic.

Ocular-CNS type

This is the most common type and is a uveitis “masquerade” syndrome.

Clinical features

•Typical: “vitritis” (cellular infiltrate), yellowish sub-RPE plaques with overlying pigment clumping; 90% bilateral.

•Atypical: may mimic CMV retinitis, ARN, and uveitis associated with sarcoidosis, TB, and syphilis.

Systemic (or visceral) type

This is less common and has a uveal pattern of disease and a better prognosis than that of the ocular-CNS type.

Clinical features

•Typical: more diffuse yellowish choroidal thickening (may be multifocal), with minimal if any vitritis.

•Atypical: may mimic melanoma (or other choroidal tumors), posterior scleritis, unior multifocal choroiditis.

Investigation

Consider diagnostic vitrectomy, FNA or even incisional biopsy (if chorioretinal involvement) to obtain cytology and histology. Multiple vitreous biopsies may be needed to make the diagnosis. The vitreous specimen requires careful handling and should be spun down. An IL10:IL6 ratio of >1.0 performed on the specimen fluid may be suggestive of intraocular lymphoma (but is not 100% sensitive or specific).

Systemic assessment and treatment should be coordinated by an oncologist and usually includes lumbar puncture and MRI brain (for ocular-CNS type) and abdominal-pelvis imaging (for systemic type).

Treatment

Treatment options include radiotherapy (external beam or plaque) and chemotherapy (systemic or intravitreal). CNS involvement may require aggressive treatment with combined intrathecal and intravenous chemotherapy and radiotherapy.

Neuro-ophthalmology

Anatomy and physiology (1) 514

Anatomy and physiology (2) 516

Anatomy and physiology (3) 518

Optic neuropathy: assessment 519

Optic neuritis: assessment 522

Anterior ischemic optic neuropathy (1) 524

Anterior ischemic optic neuropathy (2) 526

Other optic neuropathies and atrophies 528

Papilledema 530

Idiopathic intracranial hypertension 533

Congenital optic disc anomalies 535

Chiasmal disorders 537

Retrochiasmal disorders 539

Migraine 541

Supranuclear eye movement disorders (1) 543

Supranuclear eye movement disorders (2) 546

Third nerve disorders 547

Fourth nerve disorders 550

Sixth nerve disorders 552

Horner’s syndrome 554

Adie’s tonic pupil 556

Nystagmus (1) 557

Nystagmus (2) 558

Saccadic oscillations and intrusions 561

Neuromuscular junction disorders 562

Myopathies 565

Blepharospasm and other dystonias 567

Functional visual loss 569

514 CHAPTER 16 Neuro-ophthalmology

Anatomy and physiology (1)

Within the retina, photoreceptors transduce photons into electrical impulses that are relayed via bipolar cells to the retinal ganglion cell. The ganglion cells can be divided into two populations: the parvocellular system for fine visual acuity and color, and the magnocellular system for motion detection and coarser form vision. This division is preserved in both the lateral geniculate nucleus and the visual cortex.

Optic nerve

The optic nerve is about 50 mm long, carries 1.2 million axons, and runs from the optic disc to the chiasm. It may be divided into the following:

•Intraocular part (1 mm long): unmyelinated axons pass through the channels of the lamina cribrosa to become myelinated, thus doubling in diameter (1.5 mm prelaminar to 3.0 mm retrolaminar).

•Intraorbital part (25 mm long): this portion has a full meningeal sheath of tough outer dura (continuous with sclera anteriorly and periosteum of sphenoid posteriorly), arachnoid, subarachnoid space, and inner pia mater. It has around 8 mm of slack to allow free ocular motility.

•Intracanalicular part (5–9 mm long): the nerve enters the optic foramen to travel through the optic canal within the lesser wing of the sphenoid.

•Intracranial part (12–16 mm long; 4.5 mm diameter): the nerve runs up, posteriorly, and medially to form the chiasm. Neighboring structures include the frontal lobes superiorly, the internal carotid artery (ICA) laterally, and the ophthalmic artery inferolaterally.

Blood supply

The ophthalmic artery originates from the ICA. It lies inferolaterally to the intracranial optic nerve and inferiorly to the intracanalicular part and perforates the intraorbital part 8–12 mm behind the globe to become the central retinal artery.

The intracranial, intracanalicular, and intraorbital portions of the optic nerve are supplied by the pial plexus fed by branches of the ophthalmic artery and, most posteriorly, by superior hypophyseal artery. The intraocular part (optic nerve head) is supplied by the circle of Zinn–Haller, an anastomosis fed mainly by the short posterior ciliary arteries.

Optic chiasm

The optic chiasm (8 mm long, 12 mm wide) represents the joining of both optic nerves, hemidecussation of the nasal fibers, and emergence of the optic tracts. The chiasm usually lies directly above the pituitary gland (80%) but may be relatively anterior (prefixed) or posterior (postfixed).

The pituitary itself lies within the sella turcica of the sphenoid, roofed by the diaphragma sellae, a sheet of dura between anterior and posterior clinoids. Neighboring structures include the cavernous sinus and ICA inferolaterally and the third ventricle lying posteriorly.

Within the chiasm, fibers from superonasal retina are found to decussate relatively posteriorly while inferonasal fibers decussate more anteriorly; some of these inferonasal fibers appear to loop so far forward as to join the contralateral optic nerve to form Wilbrand’s knee. Macular fibers decussate in the central and posterior chiasm.

ANATOMY AND PHYSIOLOGY (1) 515

Optic tract and lateral geniculate nucleus (LGN)

The optic tract runs from the chiasm to the LGN, during which axons from corresponding locations of each retina start to become associated. Within the tract, parvocellular fibers run centrally with magnocellular fibers on the outside.

The LGN is organized into six layers: contralateral fibers synapse with layers 1 (magnocellular), 4, and 6 (parvocellular); ipsilateral fibers with layers 2 (magnocellular), 3, and 5 (parvocellular). There may be other modifying pathways (akin to K cells in primates) between these layers.

Axons from superior retina synapse medially, from inferior retina laterally. Macular fibers synapse in the central and posterior LGN. The blood supply is from branches of the middle cerebral artery and thalamogeniculate branches of the posterior cerebral artery.

Optic radiation

Axons of the optic radiation project from the LGN to the visual cortex. Fibers from the superior retina project posteriorly through the parietal lobe. Fibers from the inferior retina project through the temporal lobe but deviate laterally around the inferior horn of the lateral ventricle to form Meyer’s loop. Macular fibers generally lie between these two sets of projections. The blood supply is from internal carotid, middle, and posterior cerebral arteries.

Visual cortex

The primary visual cortex (V1, Brodmann area 17, striate cortex) is located on the medial surfaces of both occipital lobes on either side of the calcarine sulcus. V1 is organized into six layers: optic tracts synapse mainly with layer IV; layers II and III project to secondary visual cortex; layer IV to superior colliculus; and layer VI back to LGN.

Superior retina is represented superiorly, inferior retina inferiorly, macula most posteriorly, and extreme temporal periphery (temporal crescent) anteriorly. The blood supply is mainly from the posterior cerebral artery but with middle cerebral artery contributions at the anterior and lateral margins.

Visual cortex cells are arranged into basic processing units representing discrete areas of the visual field. These hypercolumns comprise right and left ocular dominance columns and orientation columns. The orientation columns are divided into blobs (color) and interblobs (orientation).

Cell types range in complexity. Least discriminatory are the circularly symmetrical cells, which respond to small central stimulus regardless of orientation and movement. Simple cells require a centrally located single contrast stimulus that must be correctly orientated and moving in the correct direction. Complex cells are similar but do not require the stimulus to be centrally located. Hypercomplex cells require that the stimulus is also of a particular length.

Further processing occurs in the visual association areas, which may also integrate information from nuclei involved with head and eye movement. Subspecialization occurs in V3 (depth perception, dynamic form), V4 (color), and V5 (motion, maintenance of fixation).